Preimplantation Genetic Testing for FMR1 CGG Repeat Expansions: Clinical and Molecular Aspects in Assisted...

Fragile X syndrome is a monogenic disorder caused by the expansion of CGG trinucleotide repeats in the fragile X mental retardation 1 (FMR1) gene and is a major cause of inherited intellectual disability and reproductive impair-ment. Preimplantation genetic testing for monogenic disor-ders (PGT-M) has become an important strategy in assisted reproduction to prevent the transmission of FMR1-related disorders. This narrative review aimed to summarize cur-rent evidence on the molecular basis, technical approaches, clinical outcomes, and challenges associated with PGT-M for FMR1 CGG repeat expansions. A literature search was performed in the PubMed database, including English-lan-guage original studies, clinical investigations, and reviews. The reviewed studies demonstrate that advances in multi-plex PCR, linked-marker analysis, and next-generation se-quencing have significantly improved diagnostic accuracy, overcoming earlier limitations related to CGG repeat analy-sis, allele dropout, and mosaicism. Although women carry-ing FMR1 premutations frequently present with diminished ovarian reserve and reduced response to ovarian stimula-tion, pregnancy and live birth rates per embryo transfer are comparable to those of non-carriers when individual-ized stimulation protocols are applied. The combined ap-plication of PGT-M and Preimplantation Genetic Testing for Aneuploidy may be considered in selected clinical scenarios to optimize embryo selection, although indications should be individualized. In addition to its clinical benefits, PGT-M raises ethical, psychological, and economic considerations, emphasizing the importance of genetic counseling in re-productive decision-making. Overall, PGT-M represents a safe and effective tool in assisted reproduction for couples at risk of transmitting FMR1 related disorders, with grow-ing relevance in clinical practice and public health.